A single-chain antibody-CD39 fusion protein targeting activated platelets protects from cardiac ischaemia/reperfusion injury
Melanie Ziegler, Jan David Hohmann, Amy Kate Searle, Meike-Kristin Abraham, Harshal H Nandurkar, Xiaowei Wang, Karlheinz Peter
European Heart Journal | OXFORD UNIV PRESS | Published : 2018
Aims: CD39 is a cell membrane NTPase with anti-inflammatory and anti-platelet effects. However, its clinical use is limited by its bleeding side effect. With the goal of harnessing its therapeutic potential while avoiding haemostatic problems, we designed a fusion protein consisting of the extracellular domain of CD39 and a single-chain antibody (Targ-CD39) that specifically binds to activated glycoprotein (GP)IIb/IIIa and thus to activated platelets. Through this enrichment at activated platelets, the required systemic dose is below the dose impairing haemostasis. Methods and results: Using an ischaemia/reperfusion mouse model (left anterior descending artery ligated for 1 h) we achieved re..View full abstract
The German Research Foundation (fellowship to MZ), the National Heart Foundation of Australia (fellowship to XW) and the National Health andMedical Research Council of Australia (fellowship to K.P.).